Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review

Abstract

Rationale/methods The primary aim of the present contribution is to find a literature-based agreement on dose adjustments of vitamin C in critically ill patients undergoing renal replacement therapy (RRT). Available data/study results Critical illness is frequently accompanied by severe vitamin C deficiency. High-dose supplementation beneficially affects clinical outcome in small cohorts of patients with sepsis, burn injury, and trauma. There are no specific data on clinical outcomes in patients receiving renal replacement therapy (RRT). Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT. Vitamin C is cleared from the circulation during RRT at a rate dependent on the plasma concentration, dose and duration of RRT. Sieving coefficient is about 1. While the dose of RRT is lower than normal renal function, tubular reabsorption is absent. Sparse evidence suggests that vitamin C dosing during continuous RRT should not exceed the dose administered to critically ill patients not receiving continuous RRT. Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects. Conclusions Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose–response studies.

Wogonin alleviates liver injury in sepsis through Nrf2‐mediated NF‐κB signalling suppression

“…On the other hand, continuous oxidative stress is a potent trigger of inflammatory signalling to amplify the release of cytokines like tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) via the activation of nuclear factor‐κB (NF‐κB) pathway in hepatocytes and Kupffer cells, thus forming a positive feedback loop to recruit more neutrophils and lymphocytes and augment the damage of liver. Recently, some studies have revealed that the agents with anti‐oxidative capacity could effectively suppress the systemic immune response and improve the outcome of patients with sepsis 8,9 . However, whether septic liver injury could be relieved by the scavenging of ROS with some specific anti‐oxidative agents and thus bring benefits to sepsis treatment remains far from understood.…”

Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Biobank and Cohort Study

“…High triglycerides and low HDL cholesterol are well-established cardiovascular risk factors for progressive atherosclerosis. One described beneficial effect of vitamin C is by inhibiting lipid peroxidation in HDL, thus preserving its antioxidant activity [ 25 ], as oxidation of HDL impairs cholesterol efflux capacity and its cardioprotective effect [ 26 , 27 ]. Although differences in HDL-cholesterol between KTR according to increasing tertiles of vitamin C, with respective mean values of 1.0, 1.1, and 1.2 mmol/L, may seem numerically marginal at first sight, it should be noted that small differences in HDL cholesterol may already be associated with relatively large differences in incidence of atherosclerosis-related disease.…”

“…During a median follow-up of 9.5 (6.3-10.2) years, 75 (13%) patients developed graft failure (34,26, and 15 events over increasing tertiles of plasma vitamin C, log rank test p < 0.001). Univariate Cox proportional-hazards regression analyses of the association between tertiles of plasma vitamin C concentration and graft failure showed that patients in the highest tertile of plasma vitamin C when compared to those in the lowest tertile had a lower risk of developing graft failure (Table 2, HR 0.37; 95% CI 0.20-0.68).…”

“…Vitamin C is a recognized antioxidant and anti-inflammatory compound that attenuates oxidative stress [ 24 ], with solid pathophysiological rationale for its use in patients on renal replacement therapy and a good safety profile [ 25 , 26 ]. It inhibits lipid peroxidation in high-density lipoprotein (HDL) cholesterol [ 27 , 28 , 29 ].…”

Response to the letter of Morán et al. regarding our use of an inaccurate reference for the maximal dose of vitamin C in G6PD deficiency

“…We thank Morán et al [ 1 ] for their very attentive reading of our review on vitamin C dosing during renal replacement therapy [ 2 ], thereby noticing that one of the cited references [ 3 ] had been retracted. We used this retracted reference to support the assertion that a vitamin C dose up to 6 g/day was not contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.…”